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If you want to hear a scientist groan, ask about the grant applications he or she is writing. You are likely to hear a rant about the tight federal science budget or the belief that government grants more often fund incremental research than bold ideas. Dr. John Ioannidis of Stanford University decided to apply scientific analysis to examine how science is funded, and discover what trends lie beneath anecdotal experience.

In an analysis published Wednesday in the journal Nature, Ioannidis and Joshua M. Nicholson of Virginia Tech found that the majority of researchers who led the most influential studies — papers from the past decade that received more than 1,000 citations by other scientists — did not have current funding from the National Institutes of Health, the predominant funder of biomedical research in the United States.

That could be for a variety of reasons, but the finding that so many leading-edge scientists are not funded by the NIH raises the question, Ioannidis argues, whether the NIH encourages conformity, or even mediocrity.

For another perspective, I spoke with a scientist who is soon going to have to start thinking deeply about how life sciences research is funded: Erin K. O’Shea, a Harvard professor of molecular and cellular biology, who in January will begin a new job as chief scientific officer of the Howard Hughes Medical Institute, which provides open-ended funding to researchers, a philosophy often summed up as “people, not projects.”

Do you think there is too much conformity in how grants are awarded?

I do. . . . Consider the positive first: It works well for people who have established a track record, even as a graduate student or post-doc, and who are continuing on an expansion of the problem or something very closely related to that upon which they previously worked.

It works badly if someone tries to do something that they haven’t done before. . . . When you try to step out of the field in which you work, it is very, very difficult to get money, and I speak with firsthand experience. For 20 years I had NIH grants. I do not now and it’s in part because I changed fields.

Has the problem gotten better or worse?

My sense is this kind of conformity problem has gotten worse over the years as money gets more and more restricted and science gets bigger and bigger.

I’ve heard scientists say that the grants that do get funded are incremental. What do you think?

I absolutely think that’s right, and it’s a consequence of the way grants are judged. A large part of the judgment is whether the panel members believe the work is likely to succeed . . . where one can lay out a neatly described set of experiments and possible outcomes and a sort of flow chart of what one would do. Given this result, one would do this next. Many things in science don’t lend themselves to that type of flow chart, and in fact, some of the most interesting things do not, and the flow chart looks like a hair ball. . . .

To be fair, [the NIH] has created new models for funding, based in part on [Howard Hughes Medical Institute’s model], of funding the investigator. The NIH has several programs in that vein where they’re funding the person, in large part.